An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer

OBJECTIVE: The aim of this study was to identify the key microRNAs (miRNAs) and their regulatory networks in bladder cancer (BC). MATERIALS AND METHODS: Three miRNA and three gene expression microarray datasets were downloaded for analysis from Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were accessed by the use of GEO2R. Gene ontology process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by using the Database for Annotation, Visualization and Integrated Discovery program. Protein–protein interaction (PPI) and miRNA–mRNA regulatory networks were established by using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape tool. Besides, the results and clinical significance were validated in The Cancer Genome Atlas (TCGA) dataset. RESULTS: A total of 18 significant DEMs, 121 upregulated DEGs and 199 downregulated DEGs were identified. Functional enrichment analysis showed that significant DEGs were related to cell cycle and MAPK pathway in BC. Key DEGs such as CDK1, CCNB1, VGL and PRKCA were found as the hub genes in PPI networks. TCGA analysis supported our results, and the miRNAs were correlated with the pathological stages and survival of BC patients. CONCLUSION: In this study, we found 18 DEMs that may play key roles in the regulatory networks of BC. The higher expression of miR-99a, miR-100, miR-125b, miR-145, miR-214 and miR-487b or the lower expression of miR-138 and miR-200a can indicate poor survival in the prognosis of BC. Further experimental studies are required to test our results.